Valopicitabine Dosed in Combination with Pegylated Interferon Alfa-2a (Pegasys) Leads to Rapid Virologic Response in 93 percent of Genotype 1 Hepatitis C Patients

Idenix Pharmaceuticals announced on January 9, 2005 partial 4-week data from an ongoing phase IIb clinical trial demonstrating that treatment with valopicitabine combined with pegylated interferon alfa-2a (Pegasys) resulted in rapid and marked reduction in virus levels in treatment-naive genotype 1 hepatitis C patients. Valopicitabine is an experimental, oral nucleoside analog in development for the treatment of chronic hepatitis C.

Following are excerpts from the Idenix statement on the new partial 4-week data from the valopicitabine study:

The mean reduction in HCV levels in this trial was greater than or equal to 4 log₁₀, or 99.99 percent, after 4 weeks of treatment among patients in the two dose groups that began on Day 1 with 800 mg doses of valopicitabine. This trial is almost fully enrolled, with a target enrollment of 175 patients at more than 20 medical centers in the U.S.

These partial data will be presented at the 24th Annual JP Morgan Healthcare Conference on Wednesday, January 11 at 2:00 p.m. (PST). The conference is taking place in San Francisco, January 9-12, 2006.

"We are quite encouraged by the virologic responses demonstrated to date with these four-week data and believe that valopicitabine combined with pegylated interferon has the potential to substantially improve treatment efficacy compared to current therapy for chronic hepatitis C patients," said Jean-Pierre Sommadossi, Ph.D., chairman and chief executive officer of Idenix. "We look forward to presenting additional data from this phase IIb clinical trial in the spring and initiating a phase III clinical trial in this patient population in the second half of 2006."

This ongoing 48-week phase IIb clinical trial in treatment-naive patients includes the following five randomized treatment arms, all involving dosing regimens of valopicitabine, administered once-daily, in combination with pegylated interferon alfa-2a (Pegasys) 180 micrograms per week:

(1) Pegylated interferon beginning on Day 8 plus valopicitabine ramping from 400 mg to 800 mg beginning at Day 29;

(2) Valopicitabine 200 mg beginning on Day 1 plus pegylated interferon beginning on Day 8;

(3) Valopicitabine ramping from 400 mg to 800 mg beginning on Day 1 plus pegylated interferon beginning on Day 8;

(4) Valopicitabine 800 mg beginning on Day 1 plus pegylated interferon beginning on Day 8; and

(5) Valopicitabine 800 mg plus pegylated interferon, both beginning on Day 1.

The partial 4-week data demonstrated that the four treatment arms that included valopicitabine in combination with pegylated interferon during the first four weeks (arms B-E) all produced proportionally greater suppression of serum HCV RNA as compared to the arm that included pegylated interferon alone for the first four weeks (arm A).

At Week 4, mean HCV RNA reductions were 4.00 log10, 4.17 log10, 3.50 log₁₀ and 3.09 log₁₀, respectively, for arm E (15 patients), arm D (14 patients), arm C (18 patients) and arm B (17 patients).

In comparison, patients in the arm receiving pegylated interferon alone for the first 4 weeks (arm A, 19 patients) achieved a mean HCV RNA reduction of 2.00 log10 . The mean HCV RNA reduction for the two 800 mg dose valopicitabine arms (arms D and E) was significantly greater than that of the pegylated interferon alone arm (arm A) (p<0.01).

The addition of 800 mg of valopicitabine to pegylated interferon (arm D) led to viral clearance (PCR- negativity) in 50 percent of patients, compared to 11 percent in arm A, at Week 4.

Rapid virologic response (RVR), or a greater than or equal to 2 log₁₀ reduction in viral load by Week 4, was achieved in 93 percent of patients in the two 800 mg dose valopicitabine arms (arms D and E), indicative of a degree of virologic response which, in treatment naive patients, is thought to correlate with potentially sustained viral clearance post treatment.

Preliminary data from the first 4 weeks of treatment indicate valopicitabine continues to demonstrate adequate tolerability when administered in combination with pegylated interferon. Of the 150 patients enrolled in the trial to date, ten patients discontinued treatment by week four; nine discontinuations were due to adverse events (including 1 SAE of severe dehydration), and one for logistical reasons.

About Valopicitabine

Valopicitabine, which is administered orally once a day, is intended to block HCV replication by specifically inhibiting the HCV RNA polymerase, the enzyme that makes new copies of HCV viral chromosome inside infected cells.

Data from the phase I clinical trial sponsored by Idenix demonstrated that valopicitabine is active in patients infected with the genotype 1 strain of HCV, the strain that infects the majority of patients in North America, Europe, and Japan.

The ongoing phase II clinical trials are designed to evaluate the combination of valopicitabine and pegylated interferon in hepatitis C genotype 1 patients who previously failed to respond to antiviral treatment (nonresponders), as well as in genotype 1 patients who have not been treated previously.

Preliminary results from these phase II clinical trials to date have demonstrated that the antiviral effect of valopicitabine is enhanced when this agent is used in combination with pegylated interferon.

About Hepatitis C

Hepatitis C is an infectious liver disease caused by the hepatitis C virus. The World Health Organization estimates that 170 million individuals worldwide carry chronic HCV infection, with 3 to 4 million new infections occurring globally each year. It is the most common chronic blood-borne infection in the United States with 2.7 million chronically infected.

These "non-responders" or treatment-refractory patients comprise a growing patient population, who have no proven alternative treatments available and who are at risk for progressive HCV-associated liver disease.

As the prevalence of severe liver disease attributable to chronic hepatitis C rises, deaths due to complications from hepatitis C infection, currently 8,000 to 10,000 per year in the United States, are expected to increase dramatically over the next 15 to 20 years. (1)

For information about Idenix Pharmaceuticals, please visit http://www.idenix.com.

Additional ValopicitabineArticles on HIVandHepatitis.com

Randomized Trial of Valopicitabine (NM 283), Alone or with Peginterferon, vs Retreatment with Peginterferon Plus Ribavirin in Nonresponders to Peginterferon Alfa - 11/14/05

No Effect of Pegylated Interferon Alfa-2b (PegIntron) on the Pharmacokinetics of Valopicitabine (NM 283) in Chronic HCV Patients - 11/14/05

Potency of Novel New Nucleoside Valopicitabine Enhanced in Combination with Peginterferon in HCV Genotype in Patients with HCV Genotype 1 - 4/15/05

Pharmacokinetics and Pharmacodynamics of Valopicitabine (NM283): Results from a  Phase I/II Dose Escalation Trial - 4/15/05

Encouraging Interim Results of Phase II Study of Valopicitabine (NM-283) in Combination with Peginterferon Alfa in Patients with HCV Genotype 1  - 01/18/05

Safety, Activity and Pharmacokinetics of the Combination of New Anti-HCV Compound NM-283 Plus Pegylated Interferon 11/03/04

Roche and Pharmasset Inc Will Jointly Develop Next Generation Anti-HCV Drug PSI- 6130, an HCV Polymerase Inhibitor, in Combination with Pegasys/Copegus 10/29/03

01/10/05

Source
Idenix Pharmaceuticals. Idenix Pharmaceuticals Reports Positive 4-Week Data from a Phase IIb Clinical Trial Evaluating Valopicitabine (NM283) Combined with Pegylated Interferon in Treatment-naive Hepatitis C Patients. Press Release. January 9, 2006.

Reference
1. G Davis and others. Liver Transplantation 9(4): 331-338. 2003.